How cells feel: stochastic model for a molecular mechanosensor

Understanding mechanosensitivity, i.e. how cells sense the stiffness of their environment is very important, yet there is a fundamental difficulty in understanding its mechanism: to measure an elastic modulus one requires two points of application of force - a measuring and a reference point. The cell in contact with substrate has only one (adhesion) point to work with, and thus a new method of measurement needs to be invented. The aim of this theoretical work is to develop a self-consistent physical model for mechanosensitivity, a process by which a cell detects the mechanical stiffness of its environment (e.g. a substrate it is attached to via adhesion points) and generates an appropriate chemical signaling to remodel itself in response to this environment. The model uses the molecular mechanosensing complex of latent TGF-$\beta$ attached to the adhesion point as the biomarker. We show that the underlying Brownian motion in the substrate is the reference element in the measuring process. The model produces the closed expression for the rate of release of active TGF-$\beta$, which depends on the substrate stiffness and the pulling force coming from the cell in a subtle and non-trivial way. It is consistent with basic experimental data showing an increase in signal for stiffer substrates and higher pulling forces. In addition, we find that for each cell there is a range of stiffness where a homeostatic configuration of the cell can be achieved, outside of which the cell either relaxes its cytoskeletal forces and detaches from the very weak substrate, or generates an increasingly strong pulling force through stress fibers with a positive feedback loop on very stiff substrates. In this way, the theory offers the underlying mechanism for the myofibroblast conversion in wound healing and smooth muscle cell dysfunction in cardiac disease

Mechanosensitivity of the 2nd Kind: TGF-β Mechanism of Cell Sensing the Substrate Stiffness.

Cells can sense forces applied to them, but also the stiffness of their environment. These are two different phenomena, and here we investigate the mechanosensitivity of the 2nd kind: how the cell can measure an elastic modulus at a single point of adhesion-and how the cell can receive and interpret the chemical signal released from the sensor. Our model uses the example of large latent complex of TGF-β as a sensor. Stochastic theory gives the rate of breaking of latent complex, which initiates the signaling feedback loop after the active TGF-β release and leads to a change of cell phenotype driven by the α-smooth muscle actin. We investigate the dynamic and steady-state behaviors of the model, comparing them with experiments. In particular, we analyse the timescale of approach to the steady state, the stability of the non-linear dynamical system, and how the steady-state concentrations of the key markers vary depending on the elasticity of the substrate. We discover a crossover region for values of substrate elasticity closely corresponding to that of the fibroblast to myofibroblast transition. We suggest that the cell could actively vary the parameters of its dynamic feedback loop to 'choose' the position of the transition region and the range of substrate elasticity that it can detect. In this way, the theory offers the unifying mechanism for a variety of phenomena, such as the myofibroblast conversion in fibrosis of wounds and lungs and smooth muscle cell dysfunction in cardiac disease.This work was supported by the EPSRC Critical Mass grant for Theoretical Condensed Matter, the Sims Scholarship, and the Cambridge Trusts, and the University of Sydney.This is the final version of the article. It first appeared from PLOS via http://dx.doi.org/10.1371/journal.pone.013995

Prove di laboratorio su sonda di potenziale con elettrodo di zinco per il telecontrollo della protezione catodica

La memoria illustra i risultati di prove di laboratorio condotte su una sonda di potenziale con elettrododi zinco. L’obiettivo principale della sperimentazione è la messa a punto di un opportuno backfill per lo zincopuro in grado di assicurare la condizione di attività dello zinco e il contatto ionico con il terreno.Sono state provate miscele di gesso-bentonite-cellulosa e gesso-bentonite-fibre polimeriche.Il ponte salino è stato realizzato con membrane polimeriche ioniche e membrane cellulosiche.Sono riportati e discussi i risultati di dilavamento delle diverse composizioni di backfill e la stabilitàdella sonda in ambiente simulante terreni

Frog tendon structure and its relationship with locomotor modes

Tendon collagen fibrils are the basic force‐transmitting units of the tendon. Yet, surprisingly little is known about the diversity in tendon anatomy and ultrastructure, and the possible relationships between this diversity and locomotor modes utilized. Our main objectives were to investigate: (a) the ultra‐structural anatomy of the tendons in the digits of frogs; (b) the diversity of collagen fibril diameters across frogs with different locomotor modes; (c) the relationship between morphology, as expressed by the morphology of collagen fibrils and tendons, and locomotor modes. To assess the relationship between morphology and the locomotor modes of the sampled taxa we performed a principal component analysis considering body length, fibrillar cross sectional area (CSA) and tendon CSA. A MANOVA showed that differences between species with different locomotor modes were significant with collagen fibril diameter being the discriminating factor. Overall, our data related the greatest collagen fibril diameter to the most demanding locomotor modes, conversely, the smallest collagen fibril CSA and the highest tendon CSA were observed in animals showing a hopping locomotion requiring likely little absorption of landing forces given the short jump distances.Fil: Abdala, Virginia Sara Luz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto de Biodiversidad Neotropical. Universidad Nacional de Tucumán. Facultad de Ciencias Naturales e Instituto Miguel Lillo. Instituto de Biodiversidad Neotropical. Instituto de Biodiversidad Neotropical; ArgentinaFil: Ponssa, María Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - Tucumán. Unidad Ejecutora Lillo; ArgentinaFil: Tulli, María José. Fundación Miguel Lillo. Dirección de Zoología. Instituto de Herpetología; ArgentinaFil: Fabre, Anne Claire. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - Tucumán. Unidad Ejecutora Lillo; ArgentinaFil: Herrel, Anthony. Département D'ecologie Et de Gestion de la Biodiversité; Franci

Mechanical properties of the compass depressors of the sea-urchin Paracentrotus lividus (Echinodermata, Echinoidea) and the effects of enzymes, neurotransmitters and synthetic tensilin-like protein

The compass depressors (CDs) of the sea-urchin lantern are ligaments consisting mainly of discontinuous collagen fibrils associated with a small population of myocytes. They are mutable collagenous structures, which can change their mechanical properties rapidly and reversibly under nervous control. The aims of this investigation were to characterise the baseline (i.e. unmanipulated) static mechanical properties of the CDs of Paracentrotus lividus by means of creep tests and incremental force-extension tests, and to determine the effects on their mechanical behaviour of a range of agents. Under constant load the CDs exhibited a three-phase creep curve, the mean coefficient of viscosity being 561±365 MPa.s. The stress-strain curve showed toe, linear and yield regions; the mean strain at the toe-linear inflection was 0.86±0.61; the mean Young's modulus was 18.62±10.30 MPa; and the mean tensile strength was 8.14±5.73 MPa. Hyaluronidase from Streptomyces hyalurolyticus had no effect on creep behaviour, whilst chondroitinase ABC prolonged primary creep but had no effect on secondary creep or on any force-extension parameters; it thus appears that neither hyaluronic acid nor sulphated glycosaminoglycans have an interfibrillar load transfer function in the CD. Acetylcholine, the muscarinic agonists arecoline and methacholine, and the nicotinic agonists nicotine and 1-[1-(3,4-dimethyl-phenyl)-ethyl]-piperazine produced an abrupt increase in CD viscosity; the CDs were not differentially sensitive to muscarinic or nicotinic agonists. CDs showed either no, or no consistent, response to adrenaline, L-glutamic acid, 5-hydroxytryptamine and γ-aminobutyric acid. Synthetic echinoid tensilin-like protein had a weak and inconsistent stiffening effect, indicating that, in contrast to holothurian tensilins, the echinoid molecule may not be involved in the regulation of collagenous tissue tensility. We compare in detail the mechanical behaviour of the CD with that of mammalian tendon and highlight its potential as a model system for investigating poorly understood aspects of the ontogeny and phylogeny of vertebrate collagenous tissues.(undefined)info:eu-repo/semantics/publishedVersio

Coaches as sport workers: professional agency within the employment context of elite European basketball

Increased activity of multiple stakeholders (e.g. agents and owners) have created new challenges for some coaches working in professional sports clubs. The purpose of this project was to draw attention to the normative or accepted practices inherent in sport work, some of the day-to-day realities of some coaches working in this context, and to understand how coaches' perceptions of other stakeholders come to bear on their individual circumstances, career expectations/objectives and professional agency. Data were generated from semi-structured interviews with seven professional basketball coaches who worked in top-level European clubs. The analysis reveals the coach's relationships between some owners and agents differed with respect to exercising professional agency, and, coach's decisions and actions were tied to their professional ideals as well as understandings of what they need to undertake their work effectively and negotiation and/or adjustment strategies. Occasionally coach's work practices could be viewed as antithetical to employment security, however, the presence of insecurity was at times embraced and used strategically to affect workers' career decisions. Amid contemporary regional geo-political shifts, this work aids examinations of global sport settings, structures and issues that may contour sporting professionals' live